EE 194 Advanced VLSI Spring 2018 Tufts University Instructor: Joel Grodstein joel.grodstein@tufts.edu Lecture 8: Biological computing

EE 194/Adv. VLSI Joel Grodstein Computers are made of… Transistors. Lots of them! How many transistors on an Nvidia Volta? 21 billion! So many that we don’t really design transistors any more. We don’t even design gates. We design RTL, or assemble IP. EE 194/Adv. VLSI Joel Grodstein

A human computer is made of… Your body does a lot of computing too. What part of your body does the thinking? Brain, mostly Brains are built from … How many neurons in a brain? 100B Similar to a Volta! Is a Volta 1/5 as powerful as your brain? A transistor has one input; most gates have 2-3 inputs. A neuron can have 1000s of inputs; the brain has 100T synapses. A neuron does substantial analog computation, way more than 1 transistor Conclusion: all of us are way smarter than a Volta  neurons EE 194/Adv. VLSI Joel Grodstein

We’re not talking about brains Brains are not the only computing machines in biology Bacteria are smart, too. Really? Bacteria like to eat sugars: glucose and lactose Digesting glucose is more efficient; lactose works too Digesting each sugar requires producing specific enzymes (which cost “money;” i.e., ATP) Bacteria software: if (there is glucose around) produce glucose enzymes if (there is lactose but not glucose) produce lactose enzymes And bacteria don’t have a brain. Not one single neuron at all How can they execute this software? EE 194/Adv. VLSI Joel Grodstein

EE 194/Adv. VLSI Joel Grodstein Your body is made of… Cells. Lots of cells. 37 trillion human cells (“only” 100B neurons) many more bacterial cells (a bacteria is just one cell) What is a cell? Arguably, the smallest part that can reproduce. Which leads us to… DNA Every cell in your body has a full copy of your DNA It’s the software that makes you you. It’s the key to one type of biological computing: gene regulatory networks. EE 194/Adv. VLSI Joel Grodstein

EE 194/Adv. VLSI Joel Grodstein Your body runs on proteins The cell contains machinery to build most any protein DNA contains the data structure listing how to build various proteins DNA also contains the software that controls which proteins get built when EE 194/Adv. VLSI Joel Grodstein

The “gates” behind lactose - lacI promoter lacI The proteins lacY and lacZ help digest lactose The lac promoter says when lacY and lacZ are produced I.e., when lacI is absent and CAP is present Glucose metabolism uses up CAP LacI is produced by another stretch of DNA active only when lactose is absent Glucose → less CAP lacI - CAP + lac promoter lacY lacZ EE 194/Adv. VLSI Joel Grodstein

We can draw this as gates lacI lactose lactose - lacI promoter lacI CAP glucose The lac promoter is an AND gate The lacI promoter is inverting lactose Another inverter for glucose Glucose → less CAP lacI - CAP + lac promoter lacY lacZ CAP lacI lacY, lacZ EE 194/Adv. VLSI Joel Grodstein

EE 194/Adv. VLSI Joel Grodstein Where are the wires? Note that we did not draw any wires! VLSI chips have wires that conduct electrons exactly where we want them Chemicals move randomly in cells by diffusion Cells have no wires If we want two inverters, they had better use different chemicals! lacI lactose CAP glucose CAP lacI lacY, lacZ EE 194/Adv. VLSI Joel Grodstein

EE 194/Adv. VLSI Joel Grodstein Summary so far We have digital logic gates made from biological parts (DNA, RNA, proteins) Your body is full of these; so is a bacteria’s “body.” Every cell in your body is a sophisticated computing machine, all by itself. Every bacteria is, too None of this has anything to do with neurons or brains. EE 194/Adv. VLSI Joel Grodstein

Other digital logic in your cells Our cells have many common patterns of logic Oscillators. Any idea why? Set your 24-hour body rhythm (2017 Nobel Prize) RS latches. Create memory. Every cell in your body has memory! Delay lines, pulse generators Just-in-time manufacturing EE 194/Adv. VLSI Joel Grodstein

EE 194/Adv. VLSI Joel Grodstein So what? Well, it’s cool to understand, I think. Recombinant DNA technology We have the ability to go into a single cell and alter its DNA We can (somewhat) program a bacteria however we like Our programming ability is limited 21B transistors on a Volta A dozen or so gates in a cell (best so far) So why do we care? EE 194/Adv. VLSI Joel Grodstein

EE 194/Adv. VLSI Joel Grodstein Cells can reproduce When a cell reproduces, its altered DNA gets reproduced A bacteria may have only a dozen custom gates but that bacteria can swim in your bloodstream and reproduce How fast can bacteria reproduce? 20-30 minutes for E.coli. How many bacteria get made in 24 hours? So, about 50 generations in 24 hours. 250 is about 1015, or 1000 trillion And people are working very hard to extend that “dozen” gates up higher. EE 194/Adv. VLSI Joel Grodstein

What is the potential for this technology? Talk about cancer fighter, and recognizing the combination of multiple markers. EE 194/Adv. VLSI Joel Grodstein